Hochdurchsatz-Analyse pathogener Eigenschaften Herpesvirus-8-kodierter Gene in Endothelzellen

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Kaposi's sarcoma (KS) is an angioproliferative disease. Human herpesvirus-8 (HHV-8) has an etiologic role in KS. It is unknown, as yet, which genes of HHV-8 may trigger KS development. In this project we will systematically determine the effects of each of the 84 genes encoded by HHV-8 in primary human endothelial cell cultures. Particularly tumor relevant functions, affecting cell proliferation, adhesiveness for monocytes, migration and apoptosis will be investigated. In addition, the effect of each gene will be tested in combination with every other HHV-8 gene and with the proto-oncogenes c-myc and ras. Finally, the whole approach will be performed with endothelial cells that have been subjected to different external stimulations by inflammatory cytokines, angiogenic growth factors and the HIV-1-Tat protein. To this goal, reverse transfection of arrayed expression plasmids will be established as a high throughput transfection system which allows to determine the functions of hundreds of genes in parallel. This study will identify the genes of HHV-8 with the highest tumorigenic activation potential in endothelial cells. Moreover, our approach may provide a useful platform technology to determine the vasculopathogenic function of any set of viral and cellular genes in the scope of the Schwerpunktprogramm.